The medial septum and diagonal bands (medial septal region) is a division of the basal forebrain that is affected by aging and in particular by Alzheimer's disease. The medial septal region contains a heterogeneous population of neurons, including cholinergic and non-cholinergic projection neurons and interneurons. Even though inputs from septal neuronal populations are necessary for the normal processing of information by hippocampal and neocortical networks, only fragmented information on the anatomy, electrophysiology and pharmacology of most septal neuronal populations (cholinergic cells are the exception) is currently available. In addition, the connectivity of septal neuronal populations and their alteration with aging is fundamentally unknown. This proposal is dedicated to identify synaptic connections among septal neurons, the functional circuits established through these connections and the aging effect on septal synaptic connectivity. The proposed experiments will facilitate the modeling of normal and age-altered septal connectivity. They also may result in therapeutic strategies dedicated to modulate cognitive processes and alleviate the burden of age-related disorders, in particular Alzheimer's disease. The experimental strategy delineated in this proposal will also provide strong opportunities for intra- and inter-institutional collaborations and new career development opportunities for UTB/TSC faculty.